Tobacco smoking is one of the most common and vigorously addictive habits, negatively affecting the lives of humans, dreadfully for a very long period. It is completely transparent to observe the potential threat of smoking to the future of the health of humankind since the number of people who are smoking is expeditiously increasing [1]. Even though the number of tobacco-addicted males is currently decreasing in high-income countries, the same data shows the opposite numbers among young people and women’s tobacco usage. But eventually, 47.5% of men and 10.3% of women are currently smoking tobacco [2].
Tobacco is still leading the second main death cause title and by 2030, with today’s acceleration of usage, it can be predicted that 9 million people are going to die annually [3]. The adverse effects of tobacco smoking on the human body that causes serious harm are investigated, and in addition to that, the most globally known tobacco-related diseases caused by tobacco smoking effects on organs are COPD (Chronic Obstructive Pulmonary Disease), cancer, lung cancer, tongue cancer, and larynx cancer [4,5].

Furthermore, a series of recent researches demonstrate that extrapulmonary toxicity caused by smoking cigarettes is now also becoming important after getting sufficient data on smoking’s effects on lung health. For example, chronic diseases in organs rather than the lung can be caused by unseen and indirect repercussions of exposure to cigarette smoke constantly. However, a certain mechanism that shows how smoking has a systemic effect on diseases needs to be explained [6].

First and foremost, a single puff of cigarette smoke contains approximately 1017 oxidant molecules, and this oxidative stress caused by these molecules can be administered in various ways [7]. Either by measurements that directly calculate the oxidative stress (reactive oxygen species [ROS] production by peripheral blood cells) or as a result of oxidative stress on target molecules (producers of lipid peroxidation and oxidized proteins) or as a result of the plasma’s response to oxidative stress (antioxidant capacity) [8].
Unfortunately, only in a few investigations, the ROS production by blood cells from the circulation of smokers was used, although oxidative stress affects a variety of vital molecules more than its presence [9]–[11]. On the other hand, protein oxidation and nitration have been proposed as signs of oxidative damage. In proteins, the nitration of tyrosine results in 3-nitrotyrosine, which may serve as a marker for nitric oxide-dependent oxidative damage. So, the plasma and platelets of chronic smokers have elevated levels of 3-nitrotyrosine formed by NO and peroxynitrite [12,13]. Additionally, a study conducted by Pignatelli and coworkers showed that the levels of nitrated and oxidized fibrinogen, transferrin, plasminogen, and ceruloplasmin in smokers were significantly higher than in nonsmokers [14].
Smoking also causes a peroxidation reaction of polyunsaturated fatty acids in cell membranes, which amplifies oxidative stress. Free radical-catalyzed lipid peroxidation of arachidonic acid produces prostaglandin-like compounds known as F2-isoprostanes. Numerous studies [15]–[17] have shown that smokers produce more isoprostane 8-iso-prostaglandin F2 (PGF2) than nonsmokers. Long-term smokers, both current and former, have been reported to have significantly higher urinary 8-epiPGF2-alpha excretion than age- and sex-matched nonsmoking control subjects [18]. Moreover, between the number of cigarettes smoked and both urinary cotinine and urinary 8-epiPGF2-alpha, it can be possible to acknowledge a dose-response relationship, although isoprostanes’ biological function is not yet fully understood [16].
Also, F2 isoprostane levels were found to be considerably higher in atherosclerotic plaques than in healthy vascular tissue, indicating that these substances may be involved in disease pathogenesis [19]. This concept is supported by the discovery that patients with coronary heart disease have nearly doubled urinary 8-iso-PGF2 levels [20].
According to population-based studies, smoking status is associated with elevated levels of malondialdehyde, a degradation product of lipid peroxides [21,22]. As well, smokers have higher amounts of thiobarbituric acid reactive substances (TBARS) than nonsmokers [23]. Statistical evidence linking systemic oxidative stress with pulmonary function is presented in a population-based study [24] conducted in New York State (n 2,346). It appears that oxidative stress may have a variable effect on pulmonary function in men versus women, with Ochs-Balcom [24] and colleagues showing an inverse relationship between TBARS and predicted FEV1 and predicted FVC for men, but not for women.
Depletion of endogenous antioxidant levels in the systemic compartment is linked to exposure to oxidant compounds in smoke. Many studies have revealed that smoking lowers plasma antioxidant concentrations, and in one of the studies, smokers had considerably lower total plasma Trolox-equivalent antioxidant capacity (TEAC) than nonsmokers [13,24]. However, among healthy smokers, there was no correlation between plasma levels of TEAC and spirometric end-points (FEV1 or FEV1/FVC) [24]. Smokers’ serum levels of vitamin C, carotene, carotene, cryptoxanthin, melatonin, tocopherol, and lutein/zeaxanthin were significantly lower than nonsmokers’, according to the third National Health and Nutrition Examination Survey (NHANES) and other studies [17,25]. Nevertheless, smoking has only been demonstrated to have independent consequences on plasma levels of vitamin C and -carotene, and food may also have an impact on antioxidant levels [25]–[27].
Additionally, it has been discovered that, after adjusting for habitual dietary intake, there is an inverse correlation between smoking and plasma levels of vitamin C and beta-carotene. Such declines in plasma antioxidant levels may tend to disrupt smokers’ bodies’ natural oxidative-antioxidative equilibrium [27,28]. Surprisingly, multiple studies [29,30] have demonstrated that antioxidant supplementation only offers partial protection at best.

For instance, Glutathione (GSH) is a crucial antioxidant and has several properties such as converting peroxides into harmless hydroxyl fatty acids and/or water and maintaining the reduced and functional forms of vitamins C and E. The smoke from cigarettes oxidizes GSH to the disulfide form (oxidized glutathione), lowering the plasma GSH levels by reactive oxygen species (ROS) [31]. Also, smoking has further influences on sulfur amino acid metabolism, as shown by the even more extensive oxidation of the cysteine (Cys)/oxidized cysteine (CySS) redox pair and decreased levels of Cys [31]. This result could imply that testing the Cys/CySS redox pair may be a potentially sensitive indicator of oxidative stress in smokers, given that cysteine is the essential component for appropriate GSH production.
To put it briefly, the increased peroxides (isoprostanes and TBARS) and reduced traditional plasma antioxidants (vitamins A and C) were characterized by oxidative stress in the systemic compartment of smokers, while GSH-related antioxidants were less severely influenced [6].
Despite countless attempts to identify the biological mechanisms that may account for the established correlation between smoking and a variety of diseases and increased mortality worldwide, these mechanisms remain elusive. In addition, determining the precise mechanisms by which smoking impacts human health is a challenging scientific task and requires further studies and clinical investigations [6].
But most importantly, quitting smoking can assist with overcoming the reversible diseases caused by chronic smoking; most of them display reversible properties and can avoid the possible diseases that threaten health. Therefore, quitting smoking will help our bodies to reheal and also expand our life expectancy [1].
References:
- R. Edwards, “The problem of tobacco smoking,” BMJ, vol. 328, no. 7433, p. 217, Jan. 2004, doi: 10.1136/BMJ.328.7433.217.
- M. A. Corrao, G. E. Guindon, V. Cokkinides, and N. Sharma, “Building the evidence base for global tobacco control.,” Bull World Health Organ, vol. 78, no. 7, p. 884, 2000, Accessed: Nov. 26, 2022. [Online]. Available: /pmc/articles/PMC2560810/?report=abstract
- WHO, “The World Health Organization Report 2002: reducing risks, promoting healthy life,” WHO Library Cataloguing-in Publication Data, p. 232, 2002.
- J. Crofton and K. Bjartveit, “Smoking as a risk factor for chronic airways disease,” Chest, vol. 96, no. 3 Suppl, pp. 307S-312S, Sep. 1989, doi: 10.1378/CHEST.96.3_SUPPLEMENT.307S.
- P. Boyle, “Cancer, cigarette smoking and premature death in Europe: A review including the Recommendations of European Cancer Experts Consensus Meeting, Helsinki, October 1996,” Lung Cancer, vol. 17, no. 1, pp. 1–60, May 1997, doi: 10.1016/S0169-5002(97)00648-X.
- H. van der Vaart, D. S. Postma, W. Timens, and N. H. T. ten Hacken, “Acute effects of cigarette smoke on inflammation and oxidative stress: a review,” Thorax, vol. 59, no. 8, pp. 713–721, Aug. 2004, doi: 10.1136/THX.2003.012468.
- W. A. PRYOR and K. STONE, “Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite,” Ann N Y Acad Sci, vol. 686, no. 1, pp. 12–27, 1993, doi: 10.1111/J.1749-6632.1993.TB39148.X.
- W. MacNee, “Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease,” Proc Am Thorac Soc, vol. 2, no. 1, pp. 50–60, 2005, doi: 10.1513/PATS.200411-056SF.
- V. L. van Antwerpen et al., “Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers,” Free Radic Biol Med, vol. 18, no. 5, pp. 935–941, 1995, doi: 10.1016/0891-5849(94)00225-9.
- P. W. Ludwig and J. R. Hoidal, “Alterations in leukocyte oxidative metabolism in cigarette smokers,” Am Rev Respir Dis, vol. 126, no. 6, pp. 977–980, 1982, doi: 10.1164/ARRD.1982.126.6.977.
- S. É. Michaud, S. Dussault, P. Haddad, J. Groleau, and A. Rivard, “Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities,” Atherosclerosis, vol. 187, no. 2, pp. 423–432, 2006, doi: 10.1016/J.ATHEROSCLEROSIS.2005.10.009.
- Y. Takajo, H. Ikeda, N. Haramaki, T. Murohara, and T. Imaizumi, “Augmented oxidative stress of platelets in chronic smokers. Mechanisms of impaired platelet-derived nitric oxide bioactivity and augmented platelet aggregability,” J Am Coll Cardiol, vol. 38, no. 5, pp. 1320–1327, Nov. 2001, doi: 10.1016/S0735-1097(01)01583-2.
- S. Petruzzelli et al., “Plasma 3-nitrotyrosine in cigarette smokers,” Am J Respir Crit Care Med, vol. 156, no. 6, pp. 1902–1907, 1997, doi: 10.1164/AJRCCM.156.6.9702075.
- H. G. Dailah, “Therapeutic Potential of Small Molecules Targeting Oxidative Stress in the Treatment of Chronic Obstructive Pulmonary Disease (COPD): A Comprehensive Review,” Molecules, vol. 27, no. 17, Sep. 2022, doi: 10.3390/MOLECULES27175542.
- J. D. Morrow et al., “Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage,” N Engl J Med, vol. 332, no. 18, pp. 1198–1203, May 1995, doi: 10.1056/NEJM199505043321804.
- M. Reilly, N. Delanty, J. A. Lawson, and G. A. FitzGerald, “Modulation of oxidant stress in vivo in chronic cigarette smokers,” Circulation, vol. 94, no. 1, pp. 19–25, Jul. 1996, doi: 10.1161/01.CIR.94.1.19.
- J. Helmersson, A. Larsson, B. Vessby, and S. Basu, “Active smoking and a history of smoking are associated with enhanced prostaglandin F(2alpha), interleukin-6 and F2-isoprostane formation in elderly men,” Atherosclerosis, vol. 181, no. 1, pp. 201–207, Jul. 2005, doi: 10.1016/J.ATHEROSCLEROSIS.2004.11.026.
- C. Gniwotta, J. D. Morrow, L. J. Roberts, and H. Kuhn, “Prostaglandin F2-like compounds, F2-isoprostanes, are present in increased amounts in human atherosclerotic lesions,” Arterioscler Thromb Vasc Biol, vol. 17, no. 11, pp. 3236–3241, 1997, doi: 10.1161/01.ATV.17.11.3236.
- E. Schwedhelm et al., “Urinary 8-iso-prostaglandin F2alpha as a risk marker in patients with coronary heart disease: a matched case-control study,” Circulation, vol. 109, no. 7, pp. 843–848, Feb. 2004, doi: 10.1161/01.CIR.0000116761.93647.30.
- A. G. Rumley, M. Woodward, A. Rumley, J. Rumley, and G. D. O. Lowe, “Plasma lipid peroxides: relationships to cardiovascular risk factors and prevalent cardiovascular disease,” QJM, vol. 97, no. 12, pp. 809–816, Dec. 2004, doi: 10.1093/QJMED/HCH130.
- F. B. Smith et al., “Smoking, haemostatic factors and lipid peroxides in a population case control study of peripheral arterial disease,” Atherosclerosis, vol. 102, no. 2, pp. 155–162, 1993, doi: 10.1016/0021-9150(93)90157-P.
- H. Orhan, C. T. A. Evelo, and G. Şahin, “Erythrocyte antioxidant defense response against cigarette smoking in humans–the glutathione S-transferase vulnerability,” J Biochem Mol Toxicol, vol. 19, no. 4, pp. 226–233, 2005, doi: 10.1002/JBT.20088.
- H. M. Ochs-Balcom et al., “Oxidative stress and pulmonary function in the general population,” Am J Epidemiol, vol. 162, no. 12, pp. 1137–1145, Dec. 2005, doi: 10.1093/AJE/KWI339.
- I. Rahman, E. Swarska, W. MacNee, J. Stolk, and M. Henry, “Is there any relationship between plasma antioxidant capacity and lung function in smokers and in patients with chronic obstructive pulmonary disease?,” Thorax, vol. 55, no. 3, pp. 189–193, 2000, doi: 10.1136/THORAX.55.3.189.
- W. Wei, Y. Kim, and N. Boudreau, “Association of smoking with serum and dietary levels of antioxidants in adults: NHANES III, 1988-1994.,” Am J Public Health, vol. 91, no. 2, p. 258, 2001, doi: 10.2105/AJPH.91.2.258.
- J. Lykkesfeldt, S. Christen, L. M. Wallock, H. H. Chang, R. A. Jacob, and B. N. Ames, “Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes,” Am J Clin Nutr, vol. 71, no. 2, pp. 530–536, 2000, doi: 10.1093/AJCN/71.2.530.
- G. Schectman, J. C. Byrd, and H. W. Gruchow, “The influence of smoking on vitamin C status in adults,” Am J Public Health, vol. 79, no. 2, pp. 158–162, 1989, doi: 10.2105/AJPH.79.2.158
- K. Marangon et al., “Diet, antioxidant status, and smoking habits in French men,” Am J Clin Nutr, vol. 67, no. 2, pp. 231–239, 1998, doi: 10.1093/AJCN/67.2.231
- C. J. Fuller, M. A. May, and K. J. Martin, “The effect of vitamin E and vitamin C supplementation on LDL oxidizability and neutrophil respiratory burst in young smokers,” J Am Coll Nutr, vol. 19, no. 3, pp. 361–369, Jun. 2000, doi: 10.1080/07315724.2000.10718932.
- M. P. Pellegrini, D. E. Newby, N. R. Johnston, S. Maxwell, and D. J. Webb, “Vitamin C has no effect on endothelium-dependent vasomotion and acute endogenous fibrinolysis in healthy smokers,” J Cardiovasc Pharmacol, vol. 44, no. 1, pp. 117–124, Jul. 2004, doi: 10.1097/00005344-200407000-00016.
- S. E. Moriarty et al., “Oxidation of glutathione and cysteine in human plasma associated with smoking,” Free Radic Biol Med, vol. 35, no. 12, pp. 1582–1588, Dec. 2003, doi: 10.1016/j.freeradbiomed.2003.09.006.
Figure References:
- https://health.selfdecode.com/blog/oxidative-stress-101/
- https://news.gallup.com/poll/353225/smoking-vaping-remain-steady-low.aspx
- https://www.mdpi.com/1420-3049/27/16/5252
Inspector: Ahmet Alperen CANBOLAT